WO2005013964A1 - ナテグリニド含有製剤 - Google Patents

ナテグリニド含有製剤 Download PDF

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Publication number
WO2005013964A1
WO2005013964A1 PCT/JP2004/011711 JP2004011711W WO2005013964A1 WO 2005013964 A1 WO2005013964 A1 WO 2005013964A1 JP 2004011711 W JP2004011711 W JP 2004011711W WO 2005013964 A1 WO2005013964 A1 WO 2005013964A1
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WO
WIPO (PCT)
Prior art keywords
nateglinide
carmellose
preparation
tablet
crospovidone
Prior art date
Application number
PCT/JP2004/011711
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English (en)
French (fr)
Japanese (ja)
Inventor
Chisato Makino
Erika Motomura
Kunikazu Suzuki
Takahiko Ando
Nobutaka Ninomiya
Akira Yabuki
Original Assignee
Ajinomoto Co., Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Ajinomoto Co., Inc. filed Critical Ajinomoto Co., Inc.
Priority to JP2005513036A priority Critical patent/JP4505859B2/ja
Publication of WO2005013964A1 publication Critical patent/WO2005013964A1/ja
Priority to US11/349,225 priority patent/US7732492B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • the present invention relates to a pharmaceutical preparation containing nateglinide, which is known as a hypoglycemic agent, as an active ingredient. '
  • Nateglinide [Chemical name: N- (trans-1-isopropylcyclohexane power luponyl)]-D-phenylalanine, hereinafter referred to as nateglinide.
  • nateglinide has an excellent hypoglycemic effect upon oral administration and is known to be useful as a therapeutic agent for diabetes (Japanese Patent Publication No. 4-15221).
  • Nateglinide has the excellent property of improving postprandial hyperglycemia, and tablets with nateglinide content of 30, 60, 90, 120 or 18 Omg per tablet are actually used in clinical practice . Tablets with a nateglinide content of 60, 90, 120 or 180 mg per tablet are advantageous in that they allow a relatively large amount of active ingredient to be taken in a single dose.
  • Nateglinide 90 mg
  • for goishi tablets contains nateglinide at 25% based on the total weight of the product, 30% of low-substituted hydroxypropylcellulose as a disintegrant based on the total weight of the product, and a diameter of about 10 lmm
  • a nateglinide-containing preparation which is about 5.2 mm thick and 366 mg in weight, and which is smaller and easier to drink, has been desired (for example, W098 / 22105, W ⁇ 01 / 21159, WO 01/47557, WO 02/34254, WOO). 2/40010) o Disclosure of the invention
  • An object of the present invention is to rapidly absorb blood sugar without being affected by a meal, It is an object of the present invention to provide a tablet composition which expresses its usefulness and has a short duration without lowering the inherent properties of nateglinide and which is easier to drink.
  • the present invention relates to a preparation for oral administration containing nateglinide as an active ingredient, comprising 26% or more of nateglinide based on the total weight of the preparation, carmellose or a salt thereof, sodium carboxymethyl starch, croscarmellose sodium, crospovidone,
  • the present invention relates to a preparation characterized by containing at least one disintegrant selected from low-substituted hydroxypropylcellulose and partially pregelatinized starch in an amount of 28% or more based on the total weight of the preparation.
  • the present invention also relates to a preparation wherein the disintegrant is carmellose and / or crospovidone.
  • the present invention also relates to a preparation characterized in that the disintegrant is carmellose and crospovidone, and that the total amount of carmellose and crospovidone is 28% or more based on the weight of the preparation.
  • the present invention also relates to a preparation characterized in that the disintegrant is carmellose and crospovidone, and the total amount of carmeose and crospovidone is 33% or more based on the weight of the preparation.
  • the present invention relates to a preparation containing an acidifying agent in addition to 26% or more of nateglinide and 28% or more of a disintegrant.
  • the present invention also relates to a preparation containing a humectant in addition to 26% or more of nateglinide, 28% or more of a disintegrant and an acidifying agent.
  • the tablet composition having such a composition can reduce the size of a nateglinide-containing preparation (tablet) while maintaining the characteristic of suppressing a postprandial increase in blood glucose of nateglinide.
  • FIG. 1 is a graph showing changes in nateglinide plasma concentrations when the tablet of Example 16 and a nateglinide immediate release tablet were administered to dogs.
  • the active compound used as a hypoglycemic agent in the formulations of the present invention is nateglinide.
  • nateglinide is described, for example, in Japanese Patent Publication No. 4-152221.
  • B-type and H-type are known as crystal forms (Patent No. 2508949).
  • the crystal form used is not particularly limited irrespective of the crystal and the amorphous form as long as the size can be reduced, but the H form is preferable in terms of stability.
  • the amount of nateglinide in the preparation of the present invention must be at least 26% by weight, preferably 26 to 60% by weight, and more preferably 30 to 60% by weight in order to prepare a preparation, particularly a tablet. It is 55% by weight, particularly preferably 40 to 55%. It is preferable that the nateglinide content be in such a range, since the tablet is easy to grasp and easy to drink.
  • the disintegrant used in the present invention is any of carmellose or a salt thereof, carboxymethyl starch sodium, croscarmellose sodium, crospovidone, low-substituted hydroxypropylcellulose, and partially alpha-mono-starch.
  • a combination may be used, it is preferable to use at least two or more disintegrants in combination in order to achieve the object of the present invention.
  • the combination is not particularly limited as long as the object of the present invention can be achieved.However, by combining carmelite and crospovidone, nateglinide is contained at a high content, miniaturization is possible, and dissolution and stability are improved. Particularly preferred preparations can be produced. However, the high content of nateglinide (26% by weight or more), which is the object of the present invention,
  • the total content of these disintegrants must be at least 28% based on the total weight of the product.
  • the content of the disintegrant is preferably 35% or more.
  • the carmellose salts include calcium, magnesium, potassium and the like. 'Among these disintegrants, carmellose, crospovidone, sodium carboxymethyl starch, carmellose calcium, and carmellose potassium are preferred, and among them, carmellose and / or crospovidone are particularly preferred.
  • Carmellose is preferred for ensuring good dissolution of nateglinide over the entire physiological pH range of nateglinide, and crospovidone is preferred for ensuring good storage stability of nateglinide.
  • the combination ratio of two or more disintegrants is not particularly limited as long as the object of the present invention can be achieved.
  • the ratio of carmellose to crospovidone is 1: 1 It is preferably from 2 to 2 to 1, and particularly preferably from 1 to 1.2 to 1.2 to 1. It is preferable that the weight ratio of carmellose to crospovidone be in such a range in order to ensure good dissolution and storage stability of nateglinide.
  • nateglinide and disintegrant contents are 51% nateglinide, 22% carmellose and 19% clospovidone. By setting the content of each component in this manner, it is preferable to ensure good dissolution and storage stability of nate glide.
  • the low-substituted hydroxypropyl cellulose used as a disintegrant in the preparation of the present invention is a hydroxypropyl ether of cellulose obtained by etherifying a very small part of the hydroxyl group of the pyranose ring of cellulose with propylenoxyside. is there.
  • dried low-substituted hydroxypropylcellulose is quantified, it is a compound containing 5.0 to 16.0% by weight of a hydroxypropoxyl group (Japanese Pharmacopoeia No. 13 Revised D-885) ⁇ D-8888 and US Pharmacopoeia No. 23rd Amendment No. 253-2-254.
  • low-substituted hydroxypropylcellulose examples include: For example, low-substituted hydroxypropylcellulose L-HPC (LH-11, LH-20, LH-21, LH-22, LH-30, LH-31, LH-32) manufactured by Shin-Etsu Chemical Co., Ltd. be able to.
  • L-HPC low-substituted hydroxypropylcellulose L-HPC (LH-11, LH-20, LH-21, LH-22, LH-30, LH-31, LH-32) manufactured by Shin-Etsu Chemical Co., Ltd. be able to.
  • the preparation of the present invention further contains an acidifying agent in addition to the above composition.
  • the acidifying agent include organic acids and the like. Among them, glutamate hydrochloride, citric acid, ascorbic acid, and tartaric acid are preferable, and cunic acid and glutamic acid hydrochloride are particularly preferable. These may be used alone or in combination.
  • the acidifying agent is preferably contained at 5% or more, more preferably 5 to 20%, based on the total weight of the preparation of the present invention. It is preferable that the acidifying agent is contained in such an amount in such a range, because the rapid release of nateglinide can be ensured.
  • the pH when 1 g of the acidifying agent is dissolved in 10 OmL of purified water is preferably 3 or less, more preferably 1.5 to 2.5. Preferably it is.
  • the preparation of the present invention contains a humectant in addition to the above composition.
  • the wetting agent include a surfactant and an inorganic salt, and among them, anhydrous diacid silicon is preferable.
  • the humectant is preferably contained in an amount of preferably 1% or more, more preferably 5 to 20%, based on the total weight of the preparation of the present invention. It is preferable that the humectant is contained in such an amount in such a range, because quick release of nateglide can be ensured.
  • the tablet composition of the present invention further contains, as excipients, lactose, starch, crystalline cellulose, calcium hydrogen phosphate, light calcium anhydride, titanium oxide, and magnesium aluminate metasilicate in addition to the above essential components. can do.
  • lactose is preferred in that it does not easily cause compounding with the compound (1).
  • the amount of the excipient is 0-72% by weight, preferably 20-70% by weight, and more preferably 30-60% by weight.
  • -Furthermore it is preferable to add 0.1 to 5% by weight, preferably 0.5 to 4% by weight of hydroxypropylcellulose as a binder, because granulation becomes easy during the production process. preferable.
  • the hydroxypropylcellulose used herein is distinguished from the above-mentioned low-substituted hydroxypropylcellulose, and contains 53.4-77.5% by weight of hydroxypropoxyl group when the dried product is quantified. It is a compound (see Japanese Pharmacopoeia, 13th revision D-880-D-885, and the United States Pharmacopeia 23rd revision, page 2253).
  • Such hydroxypropyl cellulose can be obtained, for example, as hydroxypropyl cellulose HPC-L, L (fine powder) manufactured by Nippon Soda Co., Ltd.
  • additives usually used in tablet compositions can be used within a range not to impair the effects of the present invention.
  • Such additives include excipients such as microcrystalline cellulose, calcium hydrogen phosphate, starch, light silica anhydride, titanium oxide, magnesium aluminate metasilicate, polyethylene glycol, sugars (eg, lactose, mannitol) and the like.
  • Disintegrants such as starch, microcrystalline cellulose, hydroxypropyl starch, binders such as gelatin, acacia, ethylcellulose, polyvinyl alcohol, lubricants such as stearic acid, magnesium stearate, calcium stearate, talc, hardened oil, Hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose perfluoroester, polyvinyl acetate leucylaminoacetate, amino Coating agents such as alkyl methacrylate copolymers, polyvinyl acetate phthalate, polyethylene glycol (for example, macrogol), coloring agents such as evening dyes and titanium oxide, citric acid, adipic acid, ascorbic acid, and menthol Flavoring agents such as monostearic acid, glycerin, polysorbates (eg polysorbate 60, polysorbate 65, polysorbate 80), sodium lauryl sulf
  • the preparation of the present invention can be produced by a general granulation method.
  • Nateglinide The above-mentioned disintegrant and, if necessary, other additives are weighed so as to fall within the scope of the present invention, sufficiently mixed, and then granulated with water which may contain a lower alcohol such as ethanol or isopropanol, and granulated. After drying and sizing if necessary, the mixture is compressed into tablets using a tableting machine. If desired, it may be coated.
  • the nateglinide-containing tablet of the present invention thus produced is rapidly disintegrated in the gastrointestinal tract after oral administration of a conventionally known nateglinide-containing formulation, is absorbed into the blood, and improves postprandial hyperglycemia. It has become possible to reduce the size of the drug product while maintaining the above effect.
  • a goishi tablet containing 9 Omg of nateglinide has a diameter of 7.5mn! ⁇ 8.5mm, thickness 3.5mn! It is now possible to manufacture preparations of up to 4.9 mm and a volume of 122 mm 3 to 228 mm 3 , making it easier to drink in each step compared to known nateglinide-containing preparations in terms of ease of drinking.
  • the formulations of the present invention preferably have a total mass of 164-30 Omg, more preferably 165-225 mg.
  • the amount of nateglinide per tablet is 6 Omg or more, specifically 60, 90, 120 or 18 Omg. Most preferably, it is 9 Omg.
  • the nateglinide content per tablet is preferably 35% by mass or more, preferably 50 to 70% by mass, and more preferably 55 to 65% by mass. Preferably the total mass is between 100 and 25 Omg, preferably between 130 and 180 mg.
  • the amount of nateglinide is preferably 6 Omg or more, and the total mass is preferably 100 to 25 Omg.
  • the amount of nateglinide per tablet is 9 Omg, and the total mass is 130-
  • the granulated granules were subjected to extrusion granulation and subjected to a granulizer treatment to obtain granules.
  • the granulated granules were dried by fluidized bed drying until the exhaust gas temperature became 50 ° C or higher. 500 ⁇ n by sieving!
  • the ⁇ 1400 ⁇ m fraction was collected and used as a nateglyide rapid-release preparation containing a super disintegrant (nateglinide content: 50.6%, disintegrant of the present invention: 41%, formulation mass 177.9 mg (nateglinide: 9 Omg )).
  • Example 3 Example 3
  • Nateglinide: 562.5 g, low-substituted hydroxypropylcellulose: 450.0 g were mixed in a high-speed stirring granulator (High-speed mixer, Fukae Kogyo Co.), and an aqueous solution of hydroxypropyl cellulose (1.45 w / w /) was added. : Granulation was performed by adding 1035.0 g. Furthermore, after wet sizing with a speed mill (Sekai Okada), drying was performed with a fluid bed dryer (Freund Sangyo). The obtained granules were sieved with a 850-m sieve, and only the upper portion of the granules was dry-sized using a speed mill.
  • the sieved fraction and the dry sieved fraction were mixed to obtain nate glinide granules.
  • This granulated product was mixed with 300.0 g of lactose and 150.0 g of glutamate hydrochloride, and further mixed with 22.5 g of magnesium stearate to give granules for tableting.
  • the granules for tableting were formed into tablets of 9 mm 14R 3r, 24 Omg using a single-tablet tableting machine (nateglinide: 38%).
  • Hydroxypropyl methylcellulose 80 g
  • Macrogol 6000 15.0 g
  • talc 24.0 g
  • purified water 676.0 g and dispersed.
  • 5.0 g of titanium oxide was dispersed in 200.0 g of purified water. Both were mixed to form a coating solution.
  • Example 3 The tablet obtained in Example 3 was sprayed with a coating solution using a tablet coating machine (Hyiko Ichiichi, Freund Corporation) to obtain a coated tablet (coating amount: 1.55% relative to uncoated tablet weight). ). At this time, the content of nateglinide is 38% for uncoated tablets and 37% for coated tablets.
  • Example 3 The granules of nateglinide obtained in Example 3 and 450. Og of lactose were mixed, and 22.5 g of magnesium stearate was further mixed to obtain granules for tableting.
  • the tableting granules were formed into tablets of 9 mm 14R3r, 24 Omg using a single-tablet tableting machine. Coating was performed in the same manner as in Example 4 to obtain a coated tablet. At this time Tegrinide content: uncoated tablets: 38%, coated tablets: 37%.
  • Dissolution evaluation was performed with reference to Pharmaceutical Science 452.
  • Japanese Pharmacopoeia paddle method 50 revolutions per minute
  • 90 OmL of eluate 3 types of JP1 solution containing 0.75w / v% polysorbate 80, pH6.5 phosphate buffer solution, pH7.2 phosphate buffer solution
  • the dissolution rate of the formulation obtained in Example 4 and that of the formulation obtained in Comparative Example 1 were evaluated using a 20-minute value.
  • the dissolution rates of the preparations prepared in Example 4 and Comparative Example 1 were 86% and 86% in the JP1 solution containing 0.751 ⁇ % polysorbate 80, and 93% and 48% in the pH 6.5 phosphate buffer.
  • Example 4 It was 88% and 76%, respectively, in a pH 7.2 phosphate buffer, and it was confirmed that the preparation obtained in Example 4 exhibited a sufficient dissolution rate. Therefore, oral absorption is considered to be sufficient to effectively suppress postprandial blood glucose. On the other hand, the preparation prepared in Comparative Example 1 did not exhibit a sufficient dissolution rate in the pH 6.5 phosphate buffer, and was not considered to effectively suppress postprandial blood glucose.
  • nateglinide 60.0 g of nateglinide, 7.2 g of partially alpha-starch starch, 24.0 g of carmellose, 3.6 g of croscarmellose sodium and 24.0 g of low-substituted hydroxypropylcellulose were mixed in a high-speed stirring granulator. Granulation was performed by adding 100.0 mL of water. After drying the granulated product, 1.2 g of magnesium stearate was added, and after tableting, nateglinide 75 mg content (50%), disintegrant of the present invention: 73.5 mg (49%) tablets (weight 15 Omg) ).
  • Hydroxypropyl methylcellulose 80 g, macrogol 6000: 15.0 g, and talc: 24.0 g were dissolved and dispersed in purified water: 600.0 g.
  • 5.0 g of titanium oxide was dispersed in 276.0 g of purified water. Both were mixed to form a coating solution.
  • nateglinide 120g of nateglinide, 66.5g of sodium carboxymethyls sodium, 21.8g of mannitol, 6.54g of hydroxypropylcellulose are mixed with a high-speed stirring granulator (Fukae Kogyo, High Speed Mixer Mini), and water is mixed. In addition, granulation was performed. The obtained granules were dried with a fluid bed dryer (Freund Sangyo, FLO-1) and then forcibly sieved with a 850-m sieve.
  • a fluid bed dryer Frund Sangyo, FLO-1
  • Nateglinide, 120 g, Croscarmellose sodium 86.18 g, lau 2.18 g of sodium rill sulfate and 6.55 g of hydroxypropylcellulose were mixed using a high-speed agitation granulator (Fukae Kogyo Co., Ltd., No., Mini Speed Mixer Mini), and water was added to perform granulation.
  • the obtained granules were dried by a fluid bed dryer (Freund Sangyo, FL0-1) and then forcibly sieved through a 850-m sieve.
  • Example 7 Using a tablet coating machine (Hyco One Night, Freund Sangyo), sprayed 46.9 g of the coating solution prepared in the same manner as in Example 7 onto 300 g of diluted tablets added to the tablets, and applied a coating film per tablet. Was applied so as to be 2.5 mg to obtain a coated tablet.
  • Example 7 Using a tablet coating machine (Yuichi Hiko, Freund Sangyo), sprayed 46.9 g of a coating solution prepared in the same manner as in Example 7 onto 300 g of diluted tablets added to the tablets, and coated each tablet. The coating was applied so that the film thickness was 2.5 mg to obtain a coated tablet.
  • the elution rate of each of Examples 7 to 9 and Comparative Example 2 was 78, 69, 65, 1%, and 0.5 ⁇ /% polysorbate 80 in the JP 1 solution with 0.6 ⁇ % polysorbate 80 added. 4.0 1/4 dilution 80, 82, 74, 1% in Mcllvaine buffer, 94, 76, 90, 7% in JP2 solution.
  • the preparations obtained in Examples 7, 8, and 9 have a sufficient dissolution rate. Was confirmed. Therefore, it is considered that oral absorption also shows a sufficient value to effectively suppress postprandial blood glucose.
  • the preparation prepared in Comparative Example 2 did not exhibit a sufficient dissolution rate in any of the liquids, and was not considered to effectively suppress postprandial blood glucose.
  • Nateglinide 600.1 g, carmellose 220.9 g, crospovidone 220.9 s hydroxypropylcellulose 32.73 g are mixed with a high-speed stirring granulator (Fukae Industry, high-speed mixer 10JD type), and water is added. And granulated.
  • the obtained granules are wet-pulverized with a pulverizer (Sekai Okada, New Speed Mill ND-10), dried with a fluidized-bed dryer (Freund, FLO-5) and passed through an 850 m sieve. Sieved.
  • the 850 juon fraction was ground and passed through an 850 sieve.
  • Hydroxypropyl methylcellulose 80 g, Macrogol 6000: 15.0 g, and talc: 24.0 g were dissolved and dispersed in purified water: 600.0 g. On the other hand, 5.0 g of titanium oxide was dispersed in 276.0 g of purified water. Mix both Ting solution.
  • the coating liquid (49.9 g) was sprayed onto 287 g of the tablet using a tablet coating machine (Hyco Ichiichi Mini, Freund Corporation) to obtain a coated tablet.
  • Nateglinide 600.13 g, Carmellose 220.95 g, Crospovidone 220.9 g, Hydroxypropylcellulose 32.73 g are mixed in a high-speed stirring granulator (Fukae PATEC, 10JD type), and water is added to perform granulation.
  • the obtained granules were dried with a fluid bed dryer (Freund Sangyo, Model FL0-5) and sieved with an 850 m sieve.
  • the 850-mon fraction was pulverized with a pulverizer (Sekai Okada, New Speed Mill ND-10) and passed through an 850 zm sieve.
  • Hydroxypropyl methylcellulose 80 g, macrogol 6000: 15.0 g, and talc: 24.0 g were dissolved and dispersed in purified water: 600.0 g.
  • 5.0 g of titanium oxide was dispersed in 276.0 g of purified water. Both were mixed to form a coating solution.
  • nateglinide 600.0 g of nateglinide, 140.78 g of carmellose, 140.79 g of crospovidone, and 27.68 g of hydroxypropylcellulose are mixed with a high-speed stirring granulator (Fukae PATEC, 10JD type), and water is added to produce the mixture.
  • the obtained granules were dried with a fluid bed dryer (Freund Sangyo, Model FL0-5) and sieved with a 850 m sieve.
  • the 850 mm fraction was pulverized with a pulverizer (Sei Okada, New Speed Mill ND-1 type) and passed through an 850 m sieve.
  • Hydroxypropyl methylcellulose 80 g, Macrogol 6000: 15.0 Talc: 24.0 g were dissolved and dispersed in purified water: 600.0 g. On the other hand, 5.0 g of titanium oxide was dispersed in 276.0 g of purified water. Both were mixed to form a coating solution.
  • Hydroxypropyl methylcellulose 7.2 kg, Macrogol 6000: 1.35 kg, were dissolved and dispersed in purified water: 54 kg.
  • 0.45 kg of titanium oxide and 45 g of iron sesquioxide were dispersed in 24.84 kg of purified water, and both were mixed.
  • 0.49 kg of talc was added to 20 kg of the mixture and dispersed.
  • Hydroxypropyl methylcellulose 1600 g, macrogol 6000: 300 g, and talc: 240 g were dissolved and dispersed in purified water: 12 kg.
  • 100 g of titanium oxide and 7 g of iron sesquioxide were dispersed in 5520 g of purified water, and both were mixed.
  • Nateglinide lkg, carmellose 4.05 ks crospovidone 4.05 k hydroxypropylcellulose 610.0 g were mixed with a high-speed stirring granulator (PAREC, VG-200 type), and water was added to perform granulation.
  • PAREC high-speed stirring granulator
  • the obtained granules were dried with a fluid bed dryer (C. Ure, Yuku, FD-T-4 type) and sieved with a 850-m sieve.
  • the 850 zm on fraction was pulverized with a pulverizer (Sei Okada, New Speed Mill ND-10). This operation was repeated twice to obtain about 39 kg of granules.
  • Hydroxypropyl methylcellulose: 640 g, macrogol 6000: 120 g, and talc: 192 g were dissolved and dispersed in purified water: 4800 g. Separately, 10 g of titanium oxide and 0.7 g of iron sesquioxide were dispersed in 552 g of purified water. The former was weighed to 148.3 g and the latter to 562.7 g, and the two were mixed.
  • Nateglinide immediate-release tablets contain nateglinide in an amount of 25% based on the total weight of the drug product, and as a disintegrant, low-substituted hydroxypropylcell orifice in an amount of 30% based on the total weight of the drug product.
  • Figure 1 shows the change in nateglinide plasma concentration at this time.
  • Nateglinide immediate-release key agent AUC hr (by the trapezoidal method): 85. 6 g-hr / mL, Cmax: 32. 7 ig / mL, AUC of the tablets obtained in Example 1 6.
  • ⁇ 12hr (by trapezoidal method): 81.3 zg-hr / mL Cmax: 31.1 zg / mL, confirming that the bioavailability is almost the same.
PCT/JP2004/011711 2003-08-08 2004-08-09 ナテグリニド含有製剤 WO2005013964A1 (ja)

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Application Number Priority Date Filing Date Title
JP2005513036A JP4505859B2 (ja) 2003-08-08 2004-08-09 ナテグリニド含有製剤
US11/349,225 US7732492B2 (en) 2003-08-08 2006-02-08 Nateglinide-containing preparation

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JP2003-290464 2003-08-08
JP2003290464 2003-08-08

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JP (5) JP4505859B2 (ko)
KR (2) KR100882156B1 (ko)
WO (1) WO2005013964A1 (ko)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007123021A1 (ja) * 2006-04-12 2007-11-01 Nippon Soda Co., Ltd. 徐放性錠剤の製造方法
WO2008072533A1 (ja) * 2006-12-07 2008-06-19 Daiichi Sankyo Company, Limited 固形製剤の製造方法
WO2008136392A1 (ja) * 2007-04-27 2008-11-13 Ajinomoto Co., Inc. 経口投与用製剤
US7732492B2 (en) 2003-08-08 2010-06-08 Ajinomoto Co., Inc. Nateglinide-containing preparation
JP5583659B2 (ja) * 2009-03-13 2014-09-03 富山化学工業株式会社 ６−フルオロ−３−ヒドロキシ−２−ピラジンカルボキサミド含有錠剤および造粒末
US9034860B2 (en) 2006-12-07 2015-05-19 Daiichi Sankyo Company, Limited Pharmaceutical composition containing low-substituted hydroxypropyl cellulose
JP2015205916A (ja) * 2010-03-29 2015-11-19 味の素株式会社 フェニルアラニン誘導体を含有する医薬製剤

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002034254A1 (fr) * 2000-10-24 2002-05-02 Ajinomoto Co.,Inc. Preparations contenant du nateglinide
US9790538B2 (en) 2013-03-07 2017-10-17 Apdn (B.V.I.) Inc. Alkaline activation for immobilization of DNA taggants
US10741034B2 (en) 2006-05-19 2020-08-11 Apdn (B.V.I.) Inc. Security system and method of marking an inventory item and/or person in the vicinity
BRPI0719394A2 (pt) * 2006-12-07 2015-03-31 Daiichi Sankyo Company Ltd E Ube Ind Ltd Preparação medicinal sólida
JPWO2008069262A1 (ja) * 2006-12-07 2010-03-25 第一三共株式会社 安定性が改善されたフィルムコーティング製剤
TR200801178A2 (tr) * 2008-02-22 2009-09-23 Bi̇li̇m İlaç Sanayi̇ Ti̇caret A.Ş. Nateglinid ve surfaktan-ph ayarlayıcı sistemi içeren oral tablet kompozisyonları
GB201003766D0 (en) * 2010-03-05 2010-04-21 Univ Strathclyde Pulsatile drug release
WO2013066278A1 (en) * 2011-11-03 2013-05-10 Mahmut Bilgic A process for production of pharmaceutical formulations comprising nateglinide
EP2809316A1 (en) * 2012-01-31 2014-12-10 Mahmut Bilgic Synergisctic combination comprising a meglitinide derivative and lipoic acid
US9266370B2 (en) 2012-10-10 2016-02-23 Apdn (B.V.I) Inc. DNA marking of previously undistinguished items for traceability
US9297032B2 (en) * 2012-10-10 2016-03-29 Apdn (B.V.I.) Inc. Use of perturbants to facilitate incorporation and recovery of taggants from polymerized coatings
US9963740B2 (en) 2013-03-07 2018-05-08 APDN (B.V.I.), Inc. Method and device for marking articles
EP3050560A4 (en) * 2013-09-27 2017-04-05 Daicel Corporation Intraorally disintegrable tablet comprising disintegrable granular composition
WO2015054188A1 (en) 2013-10-07 2015-04-16 Apdn (B.V.I), Inc. Multimode image and spectral reader
CA2940655C (en) 2014-03-18 2020-07-07 Apdn (B.V.I.) Inc. Encrypted optical markers for security applications
US10745825B2 (en) 2014-03-18 2020-08-18 Apdn (B.V.I.) Inc. Encrypted optical markers for security applications
US10760182B2 (en) 2014-12-16 2020-09-01 Apdn (B.V.I.) Inc. Method and device for marking fibrous materials
US10519605B2 (en) 2016-04-11 2019-12-31 APDN (B.V.I.), Inc. Method of marking cellulosic products
US10995371B2 (en) 2016-10-13 2021-05-04 Apdn (B.V.I.) Inc. Composition and method of DNA marking elastomeric material
US10920274B2 (en) 2017-02-21 2021-02-16 Apdn (B.V.I.) Inc. Nucleic acid coated submicron particles for authentication

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10194969A (ja) * 1996-11-15 1998-07-28 Ajinomoto Co Inc 錠剤組成物
JPH11514001A (ja) * 1996-07-01 1999-11-30 ファイザー・インク バージニアマイシン混合物
JP2000351732A (ja) * 1999-06-07 2000-12-19 Taisho Pharm Ind Ltd 水分散性良好なアシクロビル含有錠剤
JP2002087960A (ja) * 2000-07-14 2002-03-27 Toyama Chem Co Ltd 徐放性錠剤
WO2002034254A1 (fr) * 2000-10-24 2002-05-02 Ajinomoto Co.,Inc. Preparations contenant du nateglinide
WO2002040010A1 (fr) * 2000-10-24 2002-05-23 Ajinomoto Co.,Inc. Preparations de medicament contenant du nateglinide
JP2002173428A (ja) * 2000-12-04 2002-06-21 Taisho Pharmaceut Co Ltd クラリスロマイシン錠剤およびその製造法
JP2003505509A (ja) * 1999-08-03 2003-02-12 リリー アイコス リミテッド ライアビリティ カンパニー β−カルボリン製薬組成物
JP2003210256A (ja) * 2002-01-25 2003-07-29 Sun Wave Ind Co Ltd 回転式載置台

Family Cites Families (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2259646C2 (de) * 1972-12-06 1984-11-22 Hoechst Ag, 6230 Frankfurt Hochdosierte Tabletten von Cephalosporin-Derivaten sowie Verfahren zu ihrer Herstellung
JPS5438167B2 (ko) * 1974-04-27 1979-11-19
JPS5344618A (en) * 1976-10-04 1978-04-21 Takeda Chem Ind Ltd Preparation of tablet
ATE13486T1 (de) * 1980-11-12 1985-06-15 Ciba Geigy Ag Schnellzerfallende arzneimittel-presslinge.
EP0301006B1 (en) * 1986-04-01 1992-05-06 The Upjohn Company Methylprednisolone/sodium carboxymethyl starch tablet composition
JPH0415221A (ja) 1990-05-08 1992-01-20 Daicel Chem Ind Ltd ポリカーボネートの製造法
JPH09208468A (ja) * 1996-02-02 1997-08-12 Dainippon Pharmaceut Co Ltd ｐ−クロロ−Ｎ−（２−モルホリノエチル）ベンズアミドを含有する錠剤
WO1997031639A1 (fr) 1996-02-29 1997-09-04 Fujisawa Pharmaceutical Co., Ltd. COMPRIMES CONTENANT UN ANTIBIOTIQUE AU β-LACTAME ET PROCEDE POUR LEUR PRODUCTION
GB9613470D0 (en) 1996-06-27 1996-08-28 Ciba Geigy Ag Small solid oral dosage form
JPH10298062A (ja) * 1997-04-24 1998-11-10 Pfizer Pharmaceut Co Ltd 口腔内速溶型錠剤
JP2945001B1 (ja) * 1997-09-10 1999-09-06 大日本製薬株式会社 カーボン１３尿素含有錠
ATE481090T1 (de) * 1998-07-28 2010-10-15 Takeda Pharmaceutical Leicht zerfallende feste zubereitung
JP2000178184A (ja) * 1998-12-17 2000-06-27 Lion Corp 粒状組成物、錠剤及び粒状組成物の製造方法
US6559188B1 (en) * 1999-09-17 2003-05-06 Novartis Ag Method of treating metabolic disorders especially diabetes, or a disease or condition associated with diabetes
CO5200844A1 (es) 1999-09-17 2002-09-27 Novartis Ag Una combinacion que comprende nateglinida y cuando por menos otro compuesto antidiabetico usada para el tratamiento de desordenes metabolicos, especialmente diabetes, o de una enfermedad o condicion asociada con dibetes
RU2264811C2 (ru) 1999-12-23 2005-11-27 Новартис Аг Применение гипогликемического агента для лечения нарушенного метаболизма глюкозы
HUP0204109A3 (en) 1999-12-28 2004-06-28 Ajinomoto Kk Oral preparations for diabetes
US20010053791A1 (en) * 2000-03-16 2001-12-20 Babcock Walter C. Glycogen phosphorylase inhibitor
BR0111868A (pt) * 2000-06-22 2003-07-01 Novartis Ag Composições farmacêuticas
WO2002024230A1 (fr) 2000-09-22 2002-03-28 Takeda Chemical Industries, Ltd. Preparations solides
JP2002326925A (ja) * 2001-04-27 2002-11-15 Asahi Breweries Ltd 造粒物および錠剤の製造方法
GB0128378D0 (en) 2001-11-27 2002-01-16 Smithkline Beecham Plc Novel Compounds
JP2003201256A (ja) 2001-12-28 2003-07-18 Hisamitsu Pharmaceut Co Inc 大腸送達性経口医薬製剤、大腸癌治療用経口医薬製剤および大腸炎治療用経口医薬製剤
US6830759B2 (en) 2002-06-28 2004-12-14 Ajinomoto Co., Inc. Antidiabetic preparation for oral administration
KR100882156B1 (ko) * 2003-08-08 2009-02-06 아지노모토 가부시키가이샤 나테글리니드 함유 제제
CN1557291A (zh) 2004-01-14 2004-12-29 杨喜鸿 那格列奈分散片及其制备方法
WO2005094812A1 (ja) 2004-04-01 2005-10-13 Ajinomoto Co., Inc. ナテグリニド含有製剤
JP2008265459A (ja) 2007-04-18 2008-11-06 Daihatsu Motor Co Ltd アクスルハウジング

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11514001A (ja) * 1996-07-01 1999-11-30 ファイザー・インク バージニアマイシン混合物
JPH10194969A (ja) * 1996-11-15 1998-07-28 Ajinomoto Co Inc 錠剤組成物
JP2000351732A (ja) * 1999-06-07 2000-12-19 Taisho Pharm Ind Ltd 水分散性良好なアシクロビル含有錠剤
JP2003505509A (ja) * 1999-08-03 2003-02-12 リリー アイコス リミテッド ライアビリティ カンパニー β−カルボリン製薬組成物
JP2002087960A (ja) * 2000-07-14 2002-03-27 Toyama Chem Co Ltd 徐放性錠剤
WO2002034254A1 (fr) * 2000-10-24 2002-05-02 Ajinomoto Co.,Inc. Preparations contenant du nateglinide
WO2002040010A1 (fr) * 2000-10-24 2002-05-23 Ajinomoto Co.,Inc. Preparations de medicament contenant du nateglinide
JP2002173428A (ja) * 2000-12-04 2002-06-21 Taisho Pharmaceut Co Ltd クラリスロマイシン錠剤およびその製造法
JP2003210256A (ja) * 2002-01-25 2003-07-29 Sun Wave Ind Co Ltd 回転式載置台

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7732492B2 (en) 2003-08-08 2010-06-08 Ajinomoto Co., Inc. Nateglinide-containing preparation
WO2007123021A1 (ja) * 2006-04-12 2007-11-01 Nippon Soda Co., Ltd. 徐放性錠剤の製造方法
JP5208729B2 (ja) * 2006-04-12 2013-06-12 日本曹達株式会社 徐放性錠剤の製造方法
WO2008072533A1 (ja) * 2006-12-07 2008-06-19 Daiichi Sankyo Company, Limited 固形製剤の製造方法
US9034860B2 (en) 2006-12-07 2015-05-19 Daiichi Sankyo Company, Limited Pharmaceutical composition containing low-substituted hydroxypropyl cellulose
WO2008136392A1 (ja) * 2007-04-27 2008-11-13 Ajinomoto Co., Inc. 経口投与用製剤
JP5583659B2 (ja) * 2009-03-13 2014-09-03 富山化学工業株式会社 ６−フルオロ−３−ヒドロキシ−２−ピラジンカルボキサミド含有錠剤および造粒末
JP2015205916A (ja) * 2010-03-29 2015-11-19 味の素株式会社 フェニルアラニン誘導体を含有する医薬製剤
US10039763B2 (en) 2010-03-29 2018-08-07 Ea Pharma Co., Ltd. Pharmaceutical preparation comprising phenylalanine derivative
US10166234B2 (en) 2010-03-29 2019-01-01 Ea Pharma Co., Ltd. Pharmaceutical preparation comprising phenylalanine derivative

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US20060127475A1 (en) 2006-06-15
KR20060039934A (ko) 2006-05-09
JP4505859B2 (ja) 2010-07-21
JP4995798B2 (ja) 2012-08-08
JP4947820B2 (ja) 2012-06-06
JPWO2005013964A1 (ja) 2006-09-28
US7732492B2 (en) 2010-06-08
JP2010047612A (ja) 2010-03-04
KR20080083071A (ko) 2008-09-12
JP5282722B2 (ja) 2013-09-04
JP2009051852A (ja) 2009-03-12
JP2013014635A (ja) 2013-01-24
KR100882156B1 (ko) 2009-02-06
JP2012046534A (ja) 2012-03-08
JP5557169B2 (ja) 2014-07-23

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